| ObjectAt present,the incidence and mortality of cholangiocarcinoma are rising year by year.It is the fastest rising incidence and mortality rate in the malignant tumor of the digestive tract.It has the characteristics of occult,early diagnosis,low resection rate,insensitivity to adjuvant radiotherapy and chemotherapy,poor prognosis and so on.The clinical treatment is not ideal,and adjuvant chemotherapy is often needed after operation,but the malignant tumor of the bile duct is in chemical medicine.The multidrug resistance(MDR)phenomenon occurs during the treatment,which greatly affects the effect of the chemotherapy and the prognosis of the patients.In the protein factors closely associated with tumor multidrug resistance(MDR),SUMOylation has been identified as a key modification after translation procedures such as P53,c-Jun and HIF-1,which further affect the physiological and biochemical functions of the cells,and SUMOylation also plays a special role in the formation of multidrug resistance(MDR)in cholangiocarcinoma.In the process of producing multidrug resistance(MDR)of cholangiocarcinoma,the SUMOylation status of some proteins may change,and the physiological function changes,so it can improve their resistance to chemotherapeutic drugs.In this study,we preliminarily studied the role of SUMOylation in the formation of multidrug resistance in cholangiocarcinoma and the way to generate SUMOylation.Methods1.20 cases of cholangiocarcinoma and para-cancerous tissue were sampled and immunohistochemistry was used to detect the expression of small ubiquitinated peptide.2.The 5-FU concentration gradient induction method was used to induce cholangiocarcinoma tissue samples and construct 5-FU resistant cell lines.To compare the cell proliferation ability,cell morphology and sensitivity to cholangiocarcinoma and5-FU resistant cell lines to related chemotherapeutic drugs.3.Westren blot method was used to compare the changes of enzymes involved in the process of SUMOylation of small cholangiocarcinoma modified peptide(SUMO)protein in human cholangiocarcinoma cells,cultured cholangiocarcinoma multidrug resistance cells.Result1.20 cases of cholangiocarcinoma tissue samples of the nucleus and cytoplasm of small ubiquitinated peptide-1 were highly varying degrees of expression,adjacent tissues with or without low expression.2.Cholangiocarcinoma in the cell morphology changes,QBC939 / R and QBC939 cell proliferation was no significant difference.3.The inhibition of QBC939 was significantly higher than that of QBC939 / R when the concentration of pentafluorouracil was between 0.8 ~ 6.4 ug / mL and treated with QBC939 / R and QBC939 cells.4.At different concentrations of pentafluorouracil on QBC939 / R and QBC939 cells,there was a significant difference in the expression of these small cell ubiquitinated peptide peptides.There was no significant difference in the expression of aos-1 between QBC939 / R and QBC939 cells,and the change of uba-2 in QBC939 / R cells was related to the dosage of pentafluorouracil.The expression of senp-1 in QBC939 / R cells was significantly increased.Conclusion1.QBC939/R cell lines have significant resistance to 5-FU and cross resistance to oxaliplatin.There is a distinct difference in cell morphology between the QBC939/R cholangiocarcinoma cell line and the QBC939 cholangiocarcinoma cell line,but there is no significant difference in the cell proliferation ability.2.the multidrug resistance of the bile duct cancer is related to the changes in the state of the minor ubiquitination,which is positively related to the changes in the ubiquitination related enzymes such as uba-2 and senp-1.Therefore,the change of the state during the modification of the minor ubiquitination process can effectively prevent the production of multidrug resistance in cholangiocarcinoma. |
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